Hormones of the Pituitary

• the Anterior Lobe and
• the Posterior Lobe

The Anterior Lobe

Thyroid Stimulating Hormone (TSH)

• a beta chain of 118 amino acids and
• an alpha chain of 92 amino acids. The alpha chain is identical to that found in two other pituitary hormones, FSH and LH as well as in the hormone chorionic gonadotropin. Thus it is its beta chain that gives TSH its unique properties.

• stimulated by the arrival of thyrotropin releasing hormone (TRH) from the hypothalamus.
• inhibited by the arrival of somatostatin from the hypothalamus.

Some people develop antibodies against their own TSH receptors. When these bind the receptors, they "fool" the cell into making more T₄ causing hyperthyroidism. The condition is called thyrotoxicosis or Graves' disease.

Hormone deficiencies

A deficiency of TSH causes hypothyroidism: inadequate levels of T₄ (and thus of T₃ [Link]).

Physicians occasionally encounter patients who are homozygous for mutant TSH receptors or mutant TRH receptors. In either case, they suffer from hypothyroidism.

A deficiency of TSH, or mutant TSH receptors, have also been implicated as a cause of osteoporosis. Mice, whose TSH receptors have been knocked out, develop increased numbers of bone-reabsorbing osteoclasts.

Follicle-Stimulating Hormone (FSH)

• the same alpha chain found in TSH (and LH)
• a beta chain of 118 amino acids, which gives it its unique properties.

FSH in females

In sexually-mature females, FSH (assisted by LH) acts on the follicle to stimulate it to release estrogens.

FSH in males

Luteinizing Hormone (LH)

• the same 92-amino acid alpha subunit found in FSH and TSH (as well as in chorionic gonadotropin);
• a beta chain of 121 amino acids that is responsible for its properties.

LH in females

• a surge of LH triggers the completion of meiosis I of the egg and its release (ovulation) in the middle of the menstrual cycle;
• stimulates the now-empty follicle to develop into the corpus luteum, which secretes progesterone during the latter half of the menstrual cycle.

LH in males

LH in males is also known as interstitial cell stimulating hormone (ICSH).

Prolactin (PRL)

After birth, prolactin promotes the synthesis of milk.

• stimulated by TRH
• repressed by estrogens and dopamine.

In pregnant mice, prolactin stimulates the growth of new neurons in the olfactory center of the brain.

Growth Hormone (GH)

GH affects most of our organs, but we shall examine only its effect on growth.

• binding to receptors on the surface of liver cells.
• This stimulates them to release insulin-like growth factor-1 (IGF-1; also known as somatomedin)
• IGF-1 acts directly on the ends of the long bones promoting their growth

Things that can go wrong.

• In childhood,
  • hyposecretion of GH produces a short but normally-proportioned body.
  • Growth retardation can also result from an inability to respond to GH. This can be caused by inheriting two mutant genes encoding the receptors for
    • GHRH or
    • GH (causing Laron syndrome, a form of dwarfism) or
    • homozygosity for a disabling mutation in STAT5b, which is part of the "downstream" signaling process after GH binds its receptor.
  • hypersecretion leads to gigantism
• In adults, a hypersecretion of GH or GHRH leads to acromegaly.

Hormone-replacement therapy

GH from domestic mammals like cows and pigs does not work in humans. So for many years, the only source of GH for therapy was that extracted from the glands of human cadavers. But this supply was shut off when several patients died from a rare neurological disease attributed to contaminated glands [Link].

• boys predicted to grow no taller than 5′3″ and
• for girls, 4′11″

ACTH — the adrenocorticotropic hormone (aka corticotropin)

ACTH is a peptide of 39 amino acids. It is cut from a larger precursor proopiomelanocortin (POMC).

• glucocorticoids, like cortisol;
• mineralocorticoids, like aldosterone;
• androgens (male sex hormones, like testosterone).
• In the fetus, ACTH stimulates the adrenal cortex to synthesize a precursor of estrogen called dehydroepiandrosterone sulfate (DHEA-S) which helps prepare the mother for giving birth.

Production of ACTH depends on the intermittent arrival of corticotropin-releasing hormone (CRH) from the hypothalamus.

Hypersecretion of ACTH is a frequent cause of Cushing's disease.

Alpha Melanocyte-Stimulating Hormone (α-MSH)

MSH is discussed in a separate page. Link to it.

The Posterior Lobe

• vasopressin and
• oxytocin

Vasopressin

Vasopressin is a peptide of 9 amino acids (Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly). It is also known as arginine vasopressin (AVP), the antidiuretic hormone (ADH), and vasotocin (VT).

Vasopressin acts on the collecting ducts of the kidney to facilitate the reabsorption of water into the blood. Thus it acts to reduce the volume of urine formed (giving it its name of antidiuretic hormone).

• A deficiency of vasopressin or
• inheritance of mutant genes for its receptor (called V2)

Another type of receptor for vasopressin (designated V1a) is found in the brain, e.g., in voles and mice (rodents) and in primates like monkeys and humans.

• Male prairie voles (Microtus pinetorum) and marmoset monkeys
  • have high levels of the V1a receptor in their brains,
  • tend to be monogamous, and
  • help with care of their young.
• Male meadow voles (Microtus montanus) and rhesus monkeys
  • have lower levels of the V1a receptor in their brains,
  • are promiscuous, and
  • give little or no help with the care of their young.

Meadow voles whose brains have been injected with a vector causing increased expression of the V1a receptor become more like prairie voles in their behavior. (See Lim, M. M. et al., Nature, 17 June 2004.)

A similar shift in behavior is seen in prairie voles who cannot respond to oxytocin (below).

The level of expression of the V1a receptor gene is controlled by a "microsatellite" region upstream (5') of the ORF. This region contains from 178 to 190 copies of a repeated tetranucleotide (e.g., CAGA). Prairie voles have more copies of the repeat than meadow voles, and they express higher levels of the receptor in the parts of the brain associated with these behaviors. A similar microsatellite region is present in the pygmy chimpanzee or bonobo (Pan paniscus) but is much shorter in the less-affectionate common chimpanzee (Pan troglodytes).

Vasopressin and the Circadian Clock

Mice are nocturnal and become active at the start of the night. This is a circadian rhythm that persists for a time even after the lights in the lab are turned off each day 8 hours sooner (like arriving in London after a flight from Los Angeles, California). Only after 8–10 days do the mice overcome their "jet lag", adjusting to the new dark-light schedule. (It also takes us about one day to reset our circadian rhythms for each hour that our day-night schedule is shifted.)

It turns out that arginine vasopressin, acting on the suprachiasmatic nucleus (SCN), plays a role in this resistance to resetting their circadian clock. Mice with their genes for the V1a and V1b receptors knocked out adjust much more quickly (2–4 days) to the change. What evolutionary advantage this resistance to resetting the circadian clock confers is not clear, but understanding the mechanism raises the possibility of using drugs to speed getting over jet lag and also to help those whose work shifts are periodically altered. (Read about this work in Yamaguchi, Y., et al. in the 4 October 2013 issue of Science.)

Oxytocin

Oxytocin is a peptide of 9 amino acids (Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly).

• stimulating contractions of the uterus at the time of birth;
• stimulating release of milk when the baby begins to suckle. Mice babies born to mothers that lack oxytocin die of starvation because the mother cannot release milk.

Oxytocin is often given to prospective mothers to hasten birth.

• bonding between males and females after they have mated;
• bonding between a mother and her newborn.

In humans, oxytocin is said to increase the level of one's trust in other people.