Pulsatile secretion is a

biochemical Biochemistry, or biological chemistry, is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology, ...

phenomenon observed in a wide variety of

cell Cell most often refers to: * Cell (biology), the functional basic unit of life * Cellphone, a phone connected to a cellular network * Clandestine cell, a penetration-resistant form of a secret or outlawed organization * Electrochemical cell, a de ...

and tissue types, in which

chemical A chemical substance is a unique form of matter with constant chemical composition and characteristic properties. Chemical substances may take the form of a single element or chemical compounds. If two or more chemical substances can be combin ...

products are secreted in a regular temporal pattern. The most common cellular products observed to be released in this manner are intercellular signaling molecules such as

hormone A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physio ...

s or

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

s. Examples of hormones that are secreted pulsatilely include

insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (''INS)'' gene. It is the main Anabolism, anabolic hormone of the body. It regulates the metabol ...

, thyrotropin, TRH,

gonadotropin-releasing hormone Gonadotropin-releasing hormone (GnRH) is a releasing hormone responsible for the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. GnRH is a tropic peptide hormone synthesized and rele ...

(GnRH) and

growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in ...

(GH). In the nervous system, pulsatility is observed in oscillatory activity from

central pattern generator Central pattern generators (CPGs) are self-organizing biological neural circuits that produce rhythmic outputs in the absence of rhythmic input. They are the source of the tightly-coupled patterns of neural activity that drive rhythmic and stereo ...

s. In the heart,

pacemakers A pacemaker, also known as an artificial cardiac pacemaker, is an implanted medical device that generates electrical pulses delivered by electrodes to one or more of the chambers of the heart. Each pulse causes the targeted chamber(s) to co ...

are able to work and secrete in a pulsatile manner. A pulsatile secretion pattern is critical to the function of many hormones in order to maintain the delicate

homeostatic In biology, homeostasis (British also homoeostasis; ) is the state of steady internal physical and chemical conditions maintained by living systems. This is the condition of optimal functioning for the organism and includes many variables, su ...

balance necessary for essential life processes, such as

development Development or developing may refer to: Arts *Development (music), the process by which thematic material is reshaped * Photographic development *Filmmaking, development phase, including finance and budgeting * Development hell, when a proje ...

and

reproduction Reproduction (or procreation or breeding) is the biological process by which new individual organisms – "offspring" – are produced from their "parent" or parents. There are two forms of reproduction: Asexual reproduction, asexual and Sexual ...

. Variations of the concentration in a certain frequency can be critical to hormone function, as evidenced by the case of

GnRH agonist A gonadotropin-releasing hormone agonist (GnRH agonist) is a type of medication which affects gonadotropins and sex hormones. They are used for a variety of indications including in fertility medicine and to lower sex hormone levels in the treat ...

s, which cause functional inhibition of the receptor for GnRH due to profound

downregulation In biochemistry, in the biology, biological context of organisms' regulation of gene expression and production of gene products, downregulation is the process by which a cell (biology), cell decreases the production and quantities of its cellular ...

in response to constant (tonic) stimulation. Pulsatility may function to sensitize target tissues to the hormone of interest and

upregulate In biochemistry, in the biological context of organisms' regulation of gene expression and production of gene products, downregulation is the process by which a cell decreases the production and quantities of its cellular components, such as RNA ...

receptors, leading to improved responses. This heightened response may have served to improve the animal's fitness in its environment and promote its evolutionary retention. Pulsatile secretion in its various forms is observed in: *

Hypothalamic–pituitary–gonadal axis The hypothalamic–pituitary–gonadal axis (HPG axis, also known as the hypothalamic–pituitary–ovarian/testicular axis) refers to the hypothalamus, pituitary gland, and gonadal glands as if these individual endocrine glands were a single en ...

(HPG) related hormones *

Glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebra ...

s *

Insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (''INS)'' gene. It is the main Anabolism, anabolic hormone of the body. It regulates the metabol ...

Growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in ...

Parathyroid hormone Parathyroid hormone (PTH), also called parathormone or parathyrin, is a peptide hormone secreted by the parathyroid glands that regulates serum calcium and phosphate through its actions on the bone, kidneys, and small intestine. PTH incre ...

Neuroendocrine pulsatility

Nervous system control over hormone release is based in the

hypothalamus The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...

, from which the neurons that populate the pariventricular and

arcuate ''Arcuate'' (Latin for "curved") can refer to: Anatomy * Arcuate fasciculus * Arcuate line (disambiguation) * Arcuate artery (disambiguation), several arteries * Arcuate nucleus (hypothalamus) * Arcuate nucleus (medulla) * Arcuate ligaments of ...

nuclei originate. These neurons project to the median eminence, where they secrete releasing hormones into the hypophysial portal system connecting the hypothalamus with the

pituitary gland The pituitary gland or hypophysis is an endocrine gland in vertebrates. In humans, the pituitary gland is located at the base of the human brain, brain, protruding off the bottom of the hypothalamus. The pituitary gland and the hypothalamus contr ...

. There, they dictate endocrine function via the four HPG axes. Recent studies have begun to offer evidence that many pituitary hormones which have been observed to be released episodically are preceded by pulsatile secretion of their associated releasing hormone from the hypothalamus in a similar pulsatile fashion. Novel research into the cellular mechanisms associated with pituitary hormone pulsatility, such as that observed for

luteinizing hormone Luteinizing hormone (LH, also known as luteinising hormone, lutropin and sometimes lutrophin) is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (G ...

(LH) and

follicle-stimulating hormone Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, puberty, pubertal maturat ...

(FSH), has indicated similar pulses into the hypophyseal vessels of

(GnRH).

Luteinizing hormone and follicle-stimulating hormone (HPG axis)

LH is released from the

along with FSH in response to GnRH release into the hypophyseal portal system. Pulsatile GnRH release causes pulsatile LH and FSH release to occur, which modulates and maintains appropriate levels of

bioavailable In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...

gonadal hormone—

testosterone Testosterone is the primary male sex hormone and androgen in Male, males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testicles and prostate, as well as promoting se ...

in males and

estradiol Estradiol (E2), also called oestrogen, oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of female reproductive cycles such as estrous and menstrual cycles. Estradiol is responsible ...

in females—subject to the requirements of a superior feedback loop. In females the levels of LH is typically 1–20 IU/L during the reproductive period and is estimated to be 1.8–8.6 IU/L in males over 18 years of age.

Adrenocorticotropin and glucocorticoids (HPA axis)

Regular pulses of glucocorticoids, mainly

cortisol Cortisol is a steroid hormone in the glucocorticoid class of hormones and a stress hormone. When used as medication, it is known as hydrocortisone. Cortisol is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal corte ...

in the case of humans, are released regularly from the adrenal cortex following a

circadian A circadian rhythm (), or circadian cycle, is a natural oscillation that repeats roughly every 24 hours. Circadian rhythms can refer to any process that originates within an organism (i.e., endogenous) and responds to the environment (is entrai ...

pattern in addition to their release as a part of the

stress response The fight-or-flight or the fight-flight-freeze-or-fawn (also called hyperarousal or the acute stress response) is a physiological reaction that occurs in response to a perceived harmful event, attack, or threat to survival. It was first describ ...

Cortisol Cortisol is a steroid hormone in the glucocorticoid class of hormones and a stress hormone. When used as medication, it is known as hydrocortisone. Cortisol is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal corte ...

release follows a high frequency of pulses forming an

ultradian rhythm In chronobiology, an ultradian rhythm is a recurrent period or cycle repeated throughout a 24-hour day. In contrast, circadian rhythms complete one cycle daily, while infradian rhythms such as the menstrual cycle have periods longer than a day. ...

, with amplitude being the primary variation in its release, so that the signal is

amplitude modulated Amplitude modulation (AM) is a signal modulation technique used in electronic communication, most commonly for transmitting messages with a radio wave. In amplitude modulation, the instantaneous amplitude of the wave is varied in proportion t ...

. Glucocorticoid pulsatlity has been observed to follow a circadian rhythm, with highest levels observed before waking and before anticipated mealtimes. This pattern in amplitude of release is observed to be consistent across vertebrates. Studies done in humans, rats, and sheep have also observed a similar circadian pattern of release of

adrenocorticotropin Adrenocorticotropic hormone (ACTH; also adrenocorticotropin, corticotropin) is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important ...

(ACTH) shortly preceding the pulse in the resulting corticosteroid. It is currently hypothesized that the observed pulsatility of ACTH and glucocorticoids is driven via pulsatility of

corticotropin-releasing hormone Corticotropin-releasing hormone (CRH) (also known as corticotropin-releasing factor (CRF) or corticoliberin; corticotropin may also be spelled corticotrophin) is a peptide hormone involved in stress responses. It is a releasing hormone that b ...

(CRH), however there exist few data to support this due to difficulty in measuring CRH.

Thyrotropin and thyroid hormones (HPT axis)

The secretion pattern of thyrotropin (TSH) is shaped by

infradian In chronobiology, an infradian rhythm is a rhythm with a period longer than the period of a circadian rhythm, i.e., one cycle is longer than 24 hours. Some examples of infradian rhythms in mammals include menstrual cycle, menstruation, Sexual repro ...

, circadian and ultradian rhythms. Infradian rhythmis are mainly represented by circannual variation mirroring the seasonality of thyroid function. Circadian rhythms lead to peak ( acrophase) secretion around midnight and

nadir The nadir is the direction pointing directly ''below'' a particular location; that is, it is one of two vertical directions at a specified location, orthogonal to a horizontal flat surface. The direction opposite of the nadir is the zenith. Et ...

concentrations around noon and in the early afternoon. A similar pattern is observed for

triiodothyronine Triiodothyronine, also known as T3, is a thyroid hormone. It affects almost every physiological process in the body, including growth and development, metabolism, body temperature, and heart rate. Production of T3 and its prohormone thyroxi ...

, however with a phase shift. Pulsatile release contributes to the ultradian rhythm of TSH concentration with about 10 pulses per 24 hours. The amplitude of the circadian and ultradian rhythms is reduced in severe non-thyroidal illness syndrome (TACITUS). Contemporary theories assume that

autocrine Autocrine signaling is a form of cell signaling in which a cell secretes a hormone or chemical messenger (called the autocrine agent) that binds to autocrine receptors on that same cell, leading to changes in the cell. This can be contrasted with ...

and

paracrine In cellular biology, paracrine signaling is a form of cell signaling, a type of cellular communication (biology), cellular communication in which a Cell (biology), cell produces a signal to induce changes in nearby cells, altering the behaviour of ...

(ultrashort) feedback mechanisms controlling TSH secretion within the anterior pituitary gland are a major factor contributing to the evolution of its pulsatility.

Insulin

Pulsatile insulin secretion from individual beta cells is driven by oscillation of the calcium concentration in the cells. In beta cells lacking contact (i.e. outside islets of Lagerhans), the periodicity of these oscillations is rather variable (2–10 min). However, within an islet of Langerhans, the oscillations become synchronized by electrical coupling between closely located beta cells that are connected by

gap junctions Gap junctions are Membrane channel, membrane channels between adjacent cells that allow the direct exchange of cytoplasmic substances, such small molecules, substrates, and metabolites. Gap junctions were first described as ''close appositions' ...

, and the periodicity is more uniform (3–6 min). In addition to gap junctions, pulse coordination is managed by ATP signaling. Alpha and beta cells in the pancreas also share secrete factors in a similar pulsatile manner.

References

{{Reflist, 32em Biochemistry Cell biology Hormones Physiology Secretion